西多福韦治疗新型冠状病毒肺炎的组学预测分析

Omics prediction analysis of COVID-19 treatment with cidofovir

目的探讨西多福韦治疗新型冠状病毒肺炎的组学机制。方法应用R语言对基因表达数据库(gene expression omnibus,GEO)中西多福韦相关的全基因组表达谱开展差异分析、富集分析、蛋白互作网络分析,应用自主研发的表观精准治疗预测平台(epigenomic precision medicine prediction platform,EpiMed)筛选与西多福韦关联的疾病和药物。结果检索GEO并筛选得到GSE39293数据集,差异表达分析共筛选出585个差异表达基因,其中上调差异表达基因494个,下调差异表达基因91个。基因本体论富集条目共53条,主要与干扰病毒复制、I型干扰素作用、免疫调节等有关。京都基因与基因组百科全书富集条目共244条,主要与抗病毒、抗凋亡、免疫调节、凝血系统相关信号通路等有关。蛋白互作网络分析筛选出CDK1、CCNA2、CDC6、KIF11、MAD2L1、NDC80、RRM2、ASPM、NCAPG、CENPU为排名前10位的核心基因。EpiMed预测西多福韦调控的基因组表达谱与肺炎、严重急性呼吸综合征等疾病呈负相关,与利巴韦林、α-干扰素等药物呈正相关,与衣霉素、诺氟沙星等抗生素呈负相关。结论西多福韦能够对机体全基因组产生影响,可能通过诱导感染细胞凋亡降低体内严重急性呼吸综合征冠状病毒-2数量,通过免疫调节、凝血系统相关信号通路等对机体免疫失调及重型患者出现的凝血功能异常进行调节,达到治疗新型冠状病毒肺炎的作用。

Objective To explore the omics mechanism of cidofovir in the treatment of COVID-19.Methods The R language was used to analyze the difference,enrichment and protein interaction of cidofovir related genome-wide expression profiles in the gene expression omnibus(GEO)database,and the self-developed epigenomic precision medicine(EpiMed)prediction platform was used to filter the diseases and drugs associated with cidofovir.Results GSE39293 data sets were retrieved and filtered in GEO database.Total of 585 differentially expressed genes were screened by differential expression analysis,among which 494 genes were up-regulated and 91 genes were down-regulated.There were 53 gene ontology enrichment items,which were mainly related to interfering with virus replication,type I interferon action and immune regulation.There were 244 kyoto encyclopedia of genes and genomes enrichment items,which were mainly related to antivirus,antiapoptosis,immune regulation and coagulation system related signal pathways.CDK1,CCNA2,CDC6,KIF11,MAD2L1,NDC80,RRM2,ASPM,NCAPG and CENPU were screened as the top 10 core genes by protein interaction network analysis.EpiMed predicted that the genome expression profile regulated by cidofovir was negatively correlated with diseases such as pneumon ia and severe acute respiratory syndrome.It was positively correlated with ribavirin and alpha-interferon.It was negatively correlated with antibiotics such as chlamycin and norfloxacin.Conclusions Cidofovir can affect the whole genome of the organism and may reduce the number of SARS-COV-2 in vivo by inducing apoptosis of infected cells.Through immunoregulation and coagulation system related signaling pathways,the body’s immune disorders and coagulation dysfunction in severe patients can be regulated to achieve the effect of treating COVID-19.